Small molecule targeting of chromatin writers in cancer

Area of Science:

• Epigenetics
• Oncology
• Chemical Biology

Background:

• DNA methyltransferase and histone deacetylase inhibitors are established cancer treatments.
• The 2020 approval of the first histone methyltransferase inhibitor highlights the therapeutic potential of targeting chromatin regulation.
• DNA methylation, histone acetylation, and methylation pathways are frequently altered in human cancers, presenting numerous therapeutic targets.

Purpose of the Study:

• To review small molecule targeting approaches for epigenetic writer enzymes in cancer therapy.
• To showcase chemical probes and drug candidates for epigenetic targets.
• To suggest translational strategies for maximizing the impact of epigenetic therapies in cancer.

Main Methods:

• Literature review of small molecule targeting approaches in cancer epigenetics.
• Analysis of chemical probes and drug candidates for epigenetic writer enzymes.
• Discussion of molecular features representing epigenetic dependencies and translational strategies.

Main Results:

• The development of targeted epigenetic therapies, including histone methyltransferase inhibitors, is revitalizing cancer treatment.
• Chemical biology approaches are crucial for identifying key targets within complex epigenetic pathways.
• Numerous potentially druggable mechanisms exist within DNA methylation, histone acetylation, and methylation pathways.

Conclusions:

• Targeted manipulation of the chromatin regulatory landscape offers profound therapeutic impact in cancer.
• Small molecule targeting of epigenetic writer enzymes shows promise for novel cancer therapies.
• Translational strategies are essential to maximize the clinical benefit of epigenetic drugs in oncology.